南五加皮煎剂对小白鼠四氯化碳急性肝损伤的保护作用

目的：观察南五加皮煎剂对小白鼠四氯化碳（ CCl4）化学性肝损伤的保护作用。方法将60只健康的小白鼠均分为南五加皮煎剂小、中、大剂量组,正常组及模型组;采用注射CCl4建立小白鼠急性化学性肝损伤模型,通过测定各组动物血浆丙氨酸氨基转移酶（ ALT）活性,丙二醛（ MDA）含量及肝脏系数、肝糖原含量和观察肝脏组织病理学变化,以评价肝脏损伤程度和药物的保护作用。结果南五加皮煎剂各剂量组小白鼠血浆ALT活性、MDA含量及肝脏系数均降低,肝糖原合成增加,肝脏组织病理损伤得到明显改善,且呈明显的量效关系。结论南五加皮煎剂对CCl 4致动物急性肝损伤具有良好的保护作用。     

Beneficial effects of naringenin in liver diseases: Molecular mechanisms

Liver diseases are caused by different etiological agents, mainly alcohol consumption, viruses, drug intoxication or malnutrition. Frequently, liver diseases are initiated by oxidative stress and inflammation that lead to the excessive production of extracellular matrix(ECM), followed by a progression to fibrosis, cirrhosis and hepatocellular carcinoma(HCC). It has been reported that some natural products display hepatoprotective properties. Naringenin is a flavonoid with antioxidant, antifibrogenic, anti-inflammatory and anticancer properties that is capable of preventing liver damage caused by different agents. The main protective effects of naringenin in liver diseases are the inhibition of oxidative stress, transforming growth factor(TGF-β) pathway and the prevention of the transdifferentiation of hepatic stellate cells(HSC), leading to decreased collagen synthesis. Other effects include the inhibition of the mitogen activated protein kinase(MAPK), toll-like receptor(TLR) and TGF-β non-canonical pathways, the inhibition of which further results in a strong reduction in ECM synthesis and deposition. In addition, naringenin has shown beneficial effects on nonalcoholic fatty liver disease(NAFLD) through the regulation of lipid metabolism, modulating the synthesis and oxidation of lipids and cholesterol. Moreover, naringenin protects from HCC, since it inhibits growth factors such as TGF-β and vascular endothelial growth factor(VEGF), inducing apoptosis and regulating MAPK pathways. Naringenin is safe and acts by targeting multiple proteins. However, it possesses low bioavailability and high intestinal metabolism. In this regard, formulations, such as nanoparticles or liposomes, have been developed to improve naringenin bioavailability. We conclude that naringenin should be considered in the future as an important candidate in the treatment of different liver diseases.     

18α、18β-甘草酸及其不同配比物对CCl4肝损伤大鼠的影响

目的：研究不同配比的18α-、18β-甘草酸（GL）对四氯化碳（CCl4）肝损伤大鼠的保护作用,探讨临床应用合理比例。方法取健康雄性sD大鼠（2004-20）g70只,随机分为7组,即正常组、CCl4肝损伤组、180L—GL、18β-CL和3个不同配比组（α：13比例分别为4：6、3：7和2：8）。采用腹腔注射CCl4复制大鼠急性肝损伤模型。分别于24h和48h后摘眼球取血,测定血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、乳酸脱氢酶（LDH）活性,同时测定肝脾重量,肝脏超氧化物歧化酶（SOD）,并对肝细胞的组织形态学进行观察。结果：模型组大鼠ALT、AsT、肝脏系数显著增高,脾脏系数和SOD活性显著降低,组织病理学亦有显著差异,造模成功。5个药物组中以18α-和18β-GL配比为3：7最佳,能显著抑制CCl4引起的大鼠血清ALT、AST及肝脏系数的升高以及脾脏系数和肝脏SOD活性的降低,并能显著减轻CCl4引起的肝细胞组织病理学改变。结论：18α-与18β-GL3：7配比组对CCI。致大鼠肝损伤具有较强的保护作用,     

Differentiation of amniotic epithelial cells into various liver cell types and potential therapeutic applications

The aim of Regenerative Medicine is to replace or regenerate human cells, tissues or organs in order to restore normal function. Among all organs, the liver is endowed with remarkable regenerative capacity. Nonetheless, there are conditions in which this ability is impaired, and the use of isolated cells, including stem cells, is being considered as a possible therapeutic tool for the management of chronic hepatic disease.Placenta holds great promise for the field of regenerative medicine. It has long been used for the treatment of skin lesions and in ophthalmology, due to its ability to modulate inflammation and promote healing. More recently, cells isolated from the amniotic membrane are being considered as a possible resource for tissue regeneration, including in the context liver disease. Two cell types can be easily isolated from human amnion: epithelial cells (hAEC) and mesenchymal stromal cells (hAMSC). However only the first cell population has been demonstrated to be a possible source of proficient hepatic cells. This review will summarize current knowledge on the differentiation of hAEC into liver cells and their potential therapeutic application.     

不同浓度CCl4注射联合饮用乙醇诱导大鼠肝硬化模型研究

目的 探索不同浓度CCl4联合饮用乙醇制备大鼠肝硬化模型,寻求最佳的药物和乙醇浓度。方法 取90只SD大鼠, 分为对照组10只和实验组A组、B组、C组和D组,每组20只,给予不同浓度的CCl4油溶液腹腔注射,同时以不同浓度的乙醇溶液为饮用水,制备肝硬化模型。结果 在实验12 w末,A组大鼠死亡10只, B组死亡8只,C组死亡4只,D组死亡5只;实验A组肝细胞走向紊乱,纤维组织增生,纤维间隔形成。有假小叶形成,肝细胞大小不一,呈点灶状坏死,肝细胞凋亡、再生,汇管区内炎细胞浸润;B组与A组变化相似;C组肝细胞走向紊乱,纤维间隔形成,但无假小叶形成,肝细胞脂肪变性,纤维组织增生,肝细胞凋亡,汇管区内炎细胞浸润;D组与C组表现类似。结论 适当浓度的CCl4油溶液结合乙醇溶液为饮用水诱导大鼠肝硬化模型可显著提高造模成功率。     

Protective Effects of a Purified Saponin Mixture from Astragalus corniculatus Bieb., in vivo Hepatotoxicity Models

In this study, the in vivo effects of a purified saponin mixture (PSM), obtained from Astragalus corniculatus Bieb., were investigated using two in vivo hepatotoxicity models based on liver damage caused by paracetamol (PC) and carbon tetrachloride (CCl₄). The effects of PSM were compared with silymarin. Male Wistar rats were challenged orally with 20% CCl₄ or PC (2 g/kg) four days after being pre‐treated with PSM (100 mg/kg) or silymarin (200 mg/kg). A significant decrease of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase (LDH) activities and glutathione (GSH) levels and an increase of malondialdehyde (MDA) quantity was observed after CCl₄ and PC administration alone. PSM pre‐treatment decreased serum transaminases and LDH activities and MDA levels and increased the levels of cell protector GSH. Biotransformation phase I enzymes were also assessed in both models. In the CCl₄ hepatotoxicity model, pre‐treatment with PSM or silymarin resulted in significantly increased activities of ethylmorphine‐N‐demethylase and aniline 4‐hydroxylase activity and cytochrome P450, compared to the CCl₄ only group. Neither silymarin nor PSM influenced PC biotransformation. Our results suggest that PSM, obtained from A. corniculatus, Bieb. showed in vivo hepatoprotective and antioxidant activities against CCl₄ and PC‐induced liver damage comparable to that of silymarin. Copyright © 2012 John Wiley & Sons, Ltd.     

Anti‐apoptotic effect of San Huang Shel Shin Tang cyclodextrin complex (SHSSTc) on CCl4‐induced hepatotoxicity in rats

The metabolic loading is heavier in liver especially when injured or inflammation. San Huang Shel Shin Tang (SHSST) was an old traditional herbal decoction, which composed with Rheum officinale Baill, Scutellaria baicalnsis Geprgi and Coptis chinensis Franch (1:1:2 in weight), can provide a liver protection effects. We used a beta‐cyclodextrin (β‐CD) drug modification method in reduce of the necessary dose of the SHSST. As the results, the FAS‐FADD expressions leaded apoptosis in CCl₄ intraperitoneal (IP) injection induced acute liver injury in rats. Silymarin, baicalein, SHSST, and SHSST β‐CD complex (SHSSTc) pretreatments protected liver through the decreasing of the expressions of FAS‐FADD and downstream caspase‐3 and caspase‐8. Particularly, SHSSTc (30 mg/kg day) treatment enhanced cell survival pathway activation through the PI3K, Akt and Bad phosphorylation. Compared with SHSST as well as silymarin and baicalein, SHSSTc provided a magnificent liver protection effect, especially in survival pathway activation/TUNEL‐apoptotic cell reduction/serum cholesterol level suppression. All these data suggested that β‐CD complex modified the SHSST and promoted the bioavailability and liver protection effects. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 663–670, 2016.     

磷酸化肌球蛋白轻链在大鼠非酒精性脂肪性肝纤维化中的表达

目的探讨运用高脂饮食联合小剂量四氯化碳(CCl4)复制大鼠肝纤维化模型的特点,以及磷酸化肌球蛋白轻链[P-MLC(Thr18/Ser19)]在该纤维化模型中的作用。方法 70只SD大鼠随机分为正常对照组(N)、CCl4组(M1)和高脂饮食联合小剂量CCl4组(M2)。N组皮下注射花生油3 ml/kg,2次/周;M1组采用400 ml/L CCl4花生油混合液,3 ml/kg,2次/周皮下注射;M2组采用高脂饮食联合小剂量CCl4造模,其CCl4用量2 ml/kg,浓度和频次同M1组。造模后8周末、10周末分批处死,检测肝功能、血脂、光镜观察大鼠肝脏脂肪变性及肝纤维化程度。免疫组化法检测肝脏P-MLC的表达。结果与N组比较,8周和10周末,M1组血浆球蛋白(GLO)、谷丙转氨酶(ALT)、谷草转氨酶(AST)水平,P-MLC的表达及肝脂肪变性,纤维化程度均升高,但白球比(A/G)下降。与M1组比较,8周末,M2组ALT、AST下降,但脂肪变性增强;10周末,M2组白蛋白(ALB)、A/G下降,而ALT、AST上升明显;8周和10周末M2组P-MLC的表达及肝纤维化程度均强于M1组,差异均有统计学意义(P<0.05)。结论高脂饮食联合小剂量CCl4皮下注射复制大鼠肝纤维化模型,具有造模时间短,成功率高的优点。P-MLC的表达随着肝纤维化的进展而增加,P-MLC在非酒精性脂肪性肝纤维化中起着一定的作用。     

正交试验法优选小鼠四氯化碳矸损伤模型

目的;采用正交试验法优选小鼠四氯化碳肝损伤最佳模型制作条件,方法：选择对小鼠血清转氨酶（ALT）有影响的四个因素（1）四氯化碳浓度;（2）肝毒剂中毒剂量;（3）中毒次数;（4）中毒途径,生个因素取3个水平,按L9(3^4)正交试验表安排是试验,以阳性药联苯双酯双小鼠四氯化碳肝损伤改善率为考察指标,评定四氯化碳中毒方案的优劣,结果：采用0．1%(v/v)的四氯化碳,按每10g小鼠0.2ml剂量腹腔一次注射的给药方案为佳,结论 以正交试验法优选出的小鼠四氯化碳肝损伤模型制作方案是可行的。     

美洲大蠊醇提物对小鼠急性肝损伤的保护作用

目的 研究美洲大蠊醇提物对四氯化碳(CCl4)和刀豆蛋白A(Con A)所致小鼠肝损伤的保护作用.方法 采用ip 0.1%cch以及尾iv 20 mg,mg/kg Con A造成小鼠急性肝损伤,检测血清中ALT、AST和肝组织中SOD、MDA的水平.将肝大叶HE染色,观察美洲大蠊醇提物对小鼠肝脏组织病理学的影响.结果 ...